1. Field of the Invention
The present invention relates generally to the field of tumor biology. More specifically, the present invention relates to the use of human UDP-glucuronosyltransferase 2B7 to detect and treat cancer.
2. Description of the Related Art
UDP-glucuronosyltransferases (UGTs) comprise a family of enzymes involved in the detoxification of a variety of mostly hydrophobic endogenous and exogenous compounds. UGT isoenzymes are classified on the basis of sequence homology into two families: UGT1A and UGT2B. UGT2B enzymes catalyze the glucuronidation of bile acids, steroids, fatty acids retinoids, whereas UGT1A enzymes carry out the glucuronidation of bilirubin, phenols, various drugs and certain steroids (Radominska-Pandya et al., 1999; Jude et al., 2001). Recent studies suggested that UDP-glucuronosyltransferase proteins, in addition to their function as detoxification enzymes, are actively involved in biotransformations leading to the formation of toxic mutagens and carcinogens (Bock, 1991; Bock et al., 1999).
Environmental and other exogenous carcinogens have been implicated as a driving force for initiation of hyperproliferation and neoplastic transformation. UDP-glucuronosyltransferases play an important role in cellular detoxification and have been postulated to exert genoprotective properties.
Recent studies provided evidence for differential regulation of the UGT1A locus in human malignant and benign hepatic tumors (Strassburg et al., 1997). Functional reduction of UGT1A protein and glucuronidation activity was implicated in hepatic carcinogenesis, possibly by means of reducing cellular DNA protection. Another study examined the role of constitutional genetic variation at the UGT1A1 locus in breast cancer susceptibility. These studies suggested a link between UGT1A1 alleles, estrogen metabolism and breast cancer risk (Guillemette et al., 2000). Other evidence suggested that bilirubin plays a significant role as an antioxidant and the UGT1A1 gene plays a potential role in modulating oxidative damage and cancer (Grant & Bell, 2000).
It has been demonstrated that UDP-glucuronosyltransferase 2B7 protein was predominantly expressed in normal mammary epthelium, and that its expression was dramatically reduced in invasive breast cancers. It was postulated that UDP-glucuronosyltransferase 2B7 plays an important protective role in normal breast tissue by elimination of 4-hydroxy catecholestrogens (Gest1 et al., 2002). However, the expression and function of UDP-glucuronosyltransferase 2B7 in ovarian cancer cells have not been determined.
Human cancer tissues have the capacity to synthesize their own supply of fatty acid independent of the signals that down-regulate fatty acid synthesis in normal cells (Kuhajda, 2000). Ovarian cancer cells produce high amounts of lipid compounds including lysophospholipids, the activities of which have been linked to cancer development and metastasis (Xu et al., 2001). High level of lipid accumulation observed in ovarian cancer cells and the ability of UDP-glucuronosyltransferase 2B7 to interfere with lipid synthesis through glucuronidation of free fatty acids suggest UDP-glucuronosyltransferase 2B7 may have a role in regulating ovarian tumor cell growth.
However, the prior art is deficient in methods of using human UDP-glucuronosyltransferase 2B7 to detect and treat cancer. The present invention fulfills this long-standing need and desire in the art.